Metamizole-furosemide interaction study in healthy volunteers

The pharmacokinetic and pharmacodynamic interactions between metamizole (dipyrone) and furosemide were investigated in 9 of 12 healthy female subjects able to complete the study. They received oral metamizole 3 x 1 g for 3 days or placebo (cross-over) and on the last day of both study periods furosemide 20 mg IV. On the last two days a balanced sodium diet (120 mEq) and on Day 3 an oral water load (600 ml) were given. Metamizole significantly inhibited basal urine flow, whereas the fractional excretion of sodium and chloride and the 12 h-GFR remained unchanged. Metamizole significantly reduced furosemide clearance (175 vs 141 ml.min-1), furosemide-stimulated plasma renin activity (1.42 vs 0.79 ng AI.ml-1.h-1) and the urinary excretion of prostacyclin metabolites and of prostaglandin F2 alpha (by 70-81%). The renal clearance and terminal half-life of furosemide, peak renal chloride and volume excretion were unchanged. Thus, metamizole did not interact with the renal excretion and the diuretic effect of furosemide, although prostaglandin synthesis was significantly reduced.